Low doses of sedating antidepressants are commonly used off-label in both ME and FM to improve sleep initiation and duration.23,24 It should be noted that the effect sizes of antidepressant effects in FM are small and “a remarkable number of patients drop out of therapy because of intolerable adverse effects or experience only a small relief of symptoms, which does not outweigh the adverse effects.”21 Symptomatic management remains the mainstay of treatment.25,26

In patients with ME or FM, psychotropic medication is indicated if the psychiatric symptoms are severe enough to interfere with hope, sleep, and/or self-management. For example, a person may be so hopeless that he or she does not have the motivation to make the lifestyle changes that would improve pain and other symptoms. Psychiatric medications work best in patients with comorbid psychiatric conditions and less well when anxiety or depressive symptoms, which are reactions to adverse life events, are coincident with the ME or FM. For the comorbid group, one treats the same as for any other psychiatric patient, using current treatment guidelines. All classes of drugs, including antipsychotics, antidepressants, and mood stabilizers, are appropriate, depending on the diagnosis.

Anticonvulsants such as lamotrigine and topiramate can be helpful as mood stabilizers and because of their antinociceptive effects. Although pregabalin is effective for FM pain, gabapentin is less so. Neither has significant psychotropic properties but can be useful as a sleep aid. Buspirone is an option as an anxiolytic, but effectiveness is modest.

Because of adverse effects (eg, tolerance, withdrawal symptoms), I avoid use of benzodiazepines except in cases of severe anxiety or muscle spasm that has failed to respond to other treatment approaches. Benzodiazepines are a last choice for treatment of ME and FM.

It is accepted (though not proved) that in patients with ME and FM, psychotropic medications usually need to be started at lower doses than those tolerated by physically healthy patients. In some patients, usual therapeutic doses can be reached; in other patients, full dose is not possible because of the severity of adverse effects. Some patients are unable to tolerate any antidepressant. For these patients, there are a couple of nonpharmacological approaches that may, with care, be used alone or to augment antidepressant effects.

Eicosopentanoic acid (EPA). EPA is an omega-3 fatty acid found in fish oil. A recent meta-analysis shows that EPA is an effective treatment for MDD at dosages of 200 to 2000 mg/d.27 A recent study reported that EPA is equally as effective as fluoxetine.28 In my experience, relatively high dosages of EPA, at least 4000 mg/d, are necessary for robust antidepressant effect. EPA is not effective for anxiety. Checking the Web site of the International Fish Oil Standards Program is advised to ensure that a fish oil product meets purity standards.29

St John’s wort. This herbal remedy has strong SSRI properties and has been found to be equally as effective as SSRI drugs in treating MDD.30,31 St John’s wort is taken as a standardized 0.3% extract of hypericin 300 mg by mouth 3 times daily. It should be noted, however, that St John’s wort has many adverse effects and a long list of drugs and other herbal supplements with which it can interact adversely. In combination with other antidepressants or neurotransmitter precursors, serotonin syndrome can occur.